Complement Protein C1q Enhances Macrophage Foam Cell Survival and Efferocytosis.
Complement Protein C1q Enhances Macrophage Foam Cell Survival and Efferocytosis.
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DOI：
10.4049/jimmunol.1601445
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Fraser DA
中科院分区：
文献类型：
--
作者：
Pulanco MC;Cosman J;Ho MM;Huynh J;Fing K;Turcu J;Fraser DA
在动脉粥样硬化病变中，巨噬细胞摄取高水平的受损、修饰、低密度脂蛋白 (LDL)，产生巨噬细胞泡沫细胞。泡沫细胞会发生凋亡，如果不能通过胞吞作用有效清除，则会发生继发性坏死，导致斑块不稳定和破裂。作为先天免疫补体级联的一个组成部分，C1q 识别并调理修饰形式的 LDL，例如氧化或乙酰化 LDL，并促进体外巨噬细胞的摄取。 C1q 已被证明在体内动脉粥样硬化模型中具有保护作用。因此，这些研究旨在调查在 C1q 存在的情况下摄入修饰的 LDL 是否会改变巨噬细胞泡沫细胞的存活或功能。在一项无偏转录组分析中，C1q 被证明可以调节摄入修饰 LDL 的人类单核细胞来源的巨噬细胞中参与细胞死亡和凋亡途径的基因簇的表达，这在人类和小鼠巨噬细胞中通过定量 PCR 得到了验证。在摄入修饰的 LDL 期间，C1q 下调人和小鼠巨噬细胞中活性 caspase-3 和 PARP-1 的水平和活性。分别通过 AlamarBlue 和碘化丙啶测定法测量，这导致了存活率的显着增加和细胞死亡的减少。 C1q 调理作用还增加了巨噬细胞泡沫细胞的吞噬作用和胞吞作用。这些数据表明，C1q 在摄入过量胆固醇期间促进巨噬细胞存活，并改善泡沫细胞的细胞功能。这对于减缓疾病进展可能很重要，并有助于深入了解 C1q 在早期动脉粥样硬化中的保护作用。
In the atherosclerotic lesion, macrophages ingest high levels of damaged, modified, low density lipoproteins (LDL), generating macrophage foam cells. Foam cells undergo apoptosis, and if not efficiently cleared by efferocytosis, can undergo secondary necrosis, leading to plaque instability and rupture. As a component of the innate immune complement cascade, C1q recognizes and opsonizes modified forms of LDL such as oxidized or acetylated LDL, and promotes ingestion by macrophages in vitro. C1q has been shown to be protective in an atherosclerosis model in vivo. Therefore these studies aimed to investigate if ingestion of modified LDL in the presence of C1q would alter macrophage foam cell survival or function. In an unbiased transcriptome analysis, C1q was shown to modulate expression of clusters of genes involved in cell death and apoptosis pathways in human monocyte derived macrophages ingesting modified LDL, which were validated by quantitative PCR in both human and murine macrophages. C1q downregulated levels and activity of active caspase-3 and PARP-1 in human and mouse macrophages during ingestion of modified LDL. This led to a measurable increase in survival and decrease in cell death as measured by AlamarBlue and Propidium Iodide assays, respectively. C1q opsonization also increased phagocytosis and efferocytosis in macrophage foam cells. These data suggest that C1q promotes macrophage survival during ingestion of excess cholesterol, as well as improving foam cell efferocytic function. This may be important in slowing disease progression, and provide insight into the protective role of C1q in early atherosclerosis.
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影响因子：
5.3
作者：
Ho, Minh-Minh;Manughian-Peter, Ayla;Fraser, Deborah A.
通讯作者：
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影响因子：
6
作者：
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影响因子：
5.5
作者：
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影响因子：
5.3
作者：
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通讯作者：
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3.6
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